Palifosfamide Tromethamine(Palifosfamide Tromethamine) - 在研适应症：骨肉瘤_专利_临床

概要

基本信息

药物类型

小分子化药

别名

IPM-tris、Ifosfamide mustard、Ifosforamide mustard

+ [11]

靶点-

作用机制-

治疗领域

肿瘤皮肤和肌肉骨骼疾病其他疾病

在研适应症

骨肉瘤

非在研适应症

晚期癌症晚期恶性实体瘤晚期肉瘤+ [14]

原研机构

DEKK-TEC, Inc.

在研机构

Phoenix Children's Hospital

非在研机构

Alaunos Therapeutics, Inc.

DEKK-TEC, Inc.

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C4H11Cl2N2O2P

InChIKeyBKCJZNIZRWYHBN-UHFFFAOYSA-N

CAS号31645-39-3

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关联

13

项与 Palifosfamide Tromethamine 相关的临床试验

NCT01703754

/ Completed临床2期

A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions

Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.
Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.

开始日期2013-03-01

申办/合作机构

Alaunos Therapeutics, Inc.

NCT01808534

/ Terminated临床2期IIT

Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors

This phase II trial studies how well palifosfamide works in treating patients with recurrent germ cell tumors. Drugs used in chemotherapy, such as palifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

开始日期2013-02-01

申办/合作机构

The Indiana University School of Medicine

[+1]

NCT01555710

/ Unknown status临床3期

A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer. The MATISSE Study

This is a multinational, multicenter, randomized controlled, open-label, adaptive study to evaluate the efficacy of PaCE chemotherapy in chemotherapy naive subjects with extensive-stage SCLC. Eligible subjects will be stratified according to age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status, and randomized in a 1:1 ratio to receive either PaCE or CE chemotherapy.
The study design uses an adaptive group sequential approach with sample size re-estimation at the interim analysis.
Secondary efficacy endpoints include ORR, PFS, duration of response and changes in QOL and disease-related symptoms. Tumor-related endpoints will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
The safety of study treatments will be assessed by the frequency and severity of adverse events as determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. To provide an initial confirmation of safety, an early interim analysis of safety data only will be performed.
An independent Data Monitoring Committee (DMC) will be convened to assess the safety and efficacy of the study interventions and to monitor the overall conduct of the clinical trial.

开始日期2012-05-01

申办/合作机构

Alaunos Therapeutics, Inc.

100 项与 Palifosfamide Tromethamine 相关的临床结果

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100 项与 Palifosfamide Tromethamine 相关的转化医学

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100 项与 Palifosfamide Tromethamine 相关的专利（医药）

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55

项与 Palifosfamide Tromethamine 相关的文献（医药）

2023-04-01·Environmental science and pollution research international

Environmental performance of phytosanitary control techniques on soybean crop estimated by life cycle assessment (LCA).

Article

作者: Barizon, Robson Rolland Monticelli ; Ralisch, Ricardo ; Lucas, Kassio Ricardo Garcia ; Possamai, Edivan Jose ; Folegatti-Matsuura, Marilia Ieda da Silveira ; Ventura, Mauricio Ursi ; Mrtvi, Paulo Roberto

Phytosanitary control is essential to ensure agricultural productivity and quality. However, approaches based on scheduled use of pesticides, overuse of harmful molecules produce impacts on different types of living organisms. Integrated Pest and Disease Management (IPM-IDM) may significantly reduce the burden of pesticides in the environment. Plant resistance may also be included in the IPM-IDM and even in conventional management due to little requirement of additional knowledge and changes in agricultural practices. Robust environmental assessments using methodology of universal use, life cycle assessment (LCA), may estimate the impacts of specific pesticides that cause major damages, including remarkable category impacts. Therefore the objective of this study was to determine the impacts and (eco)toxicological effects of phytosanitary strategies (IPM-IDM including or not lepidopteran resistant transgenic cultivars) vs. the scheduled approach. Two inventory modeling methods were also applied to gather information on the use and applicability of these methods. Life cycle assessment (LCA) was applied using two inventory modeling methods: 100%Soil and PestLCI (Consensus) using data from Brazilian croplands under tropical conditions, by combining phytosanitary approaches (IPM-IDM, IPM-IDM + transgenic cultivar, conventional, conventional + transgenic cultivar) and modeling methods. Hence, eight soybean production scenarios were established. The IPM-IDM was efficient to reduce the (eco)toxicity impacts of soybean production mainly for freshwater ecotoxicity category. Due to the dynamic character of IPM-IDM approaches, the inclusion of recently introduced strategies (plant resistant and biological control to stink bugs and plant fungal diseases) may diminish even more the principal impacting substances throughout the Brazilian croplands. The PestLCI Consensus method, although its development is yet in progress, to date can be suggested to estimate the agriculture environmental impacts more properly under tropical conditions.

2021-12-01·Molecular Cancer Therapeutics2区 · 医学

Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial

2区 · 医学

Article

作者: Coindre, Jean-Michel ; Valverde, Claudia ; Gutierrez, Antonio ; Renne, Salvatore L. ; Collini, Paola ; Merlo, Domenico Franco ; Romagosa, Cleofe ; Palmerini, Emanuela ; Casali, Paolo G. ; Dei Tos, Angelo Paolo ; Bagué, Silvia ; Barisella, Marta ; Hindi, Nadia ; Braglia, Luca ; Gambarotti, Marco ; Grignani, Giovanni ; Gronchi, Alessandro ; Martin-Broto, Javier ; Velasco, Valerie ; Ramos, Rafael ; Moura, David S. ; Lopez-Pousa, Antonio ; Quagliuolo, Vittorio L. ; Brunello, Antonella ; Dopazo, Joaquin ; Blay, Jean-Yves ; Stacchiotti, Silvia ; Lopez-Lopez, Daniel ; Lopez-Alvarez, Maria ; Picci, Piero

AbstractMRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy.

2021-12-01·Journal of the Egyptian National Cancer Institute

An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart

Article

作者: Abdelhakim, Heba K ; Arafa, Hossam M M ; Mohamed, Amr S ; Ahmed, Doaa E ; Rashidi, Fatma B

AbstractBackgroundGlufosfamide (β-d-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-d-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model.MethodsCytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay.ResultsGlufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide.ConclusionsThe current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.

1

项与 Palifosfamide Tromethamine 相关的新闻（医药）

2010-06-08

·BioSpace

ZIOPHARM, Inc. Presents Positive Palifosfamide PICASSO Phase II Results in Oral Session at American Society of Clinical Oncology

NEW YORK--(BUSINESS WIRE)--ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) announced today that Dr. Claire Verschraegen of the University of New Mexico, Albuquerque and first author of the abstract, “A phase II randomized controlled trial of palifosfamide plus doxorubicin vs. doxorubicin in patients with soft tissue sarcoma (PICASSO),” (Abstract #10004) presented in an oral session today updated positive data from PICASSO. The presentation was part of the 46th Annual American Society of Clinical Oncology (ASCO) meeting being held in Chicago, IL, from June 4th to 8th. The abstract has also been selected as part of the 2010 Best of ASCO® which features high-impact abstracts from the ASCO Annual Meeting that represent the most relevant, cutting-edge science in oncology today.

ASCO会议

100 项与 Palifosfamide Tromethamine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10373	-	-	DB05668

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性软组织肉瘤	临床2期	巴拿马	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	临床2期	新加坡	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	临床2期	智利	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	临床2期	德国	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	临床2期	阿根廷	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	临床2期	加拿大	Alaunos Therapeutics, Inc.	2010-07-01
小细胞肺癌	临床2期	-	DEKK-TEC, Inc.	-
转移性软组织肉瘤	临床1期	意大利	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	药物发现	英国	Alaunos Therapeutics, Inc.	2010-07-01
转移性软组织肉瘤	药物发现	比利时	Alaunos Therapeutics, Inc.	2010-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01555710 (MATISSE, Pubmed \| J Urol) 人工标引	临床3期	广泛期小细胞肺癌	188	Palifosfamide+Carboplatin+Etoposide	(憲顧顧壓範獵繭願觸積) = 齋鹹觸積膚憲鬱築襯淵壓淵廠獵範遞鹹廠簾獵 (鬱鹽構構餘鹹積簾醖範 )	不佳	2017-08-10
				Carboplatin+Etoposide	(憲顧顧壓範獵繭願觸積) = 糧觸壓夢艱遞遞範觸積壓淵廠獵範遞鹹廠簾獵 (鬱鹽構構餘鹹積簾醖範 )
NCT01168791 (PICASSO III, Pubmed \| J Urol \| J Clin Oncol) 人工标引	临床3期	转移性软组织肉瘤	447	Doxorubicin+Palifosfamide	(製夢顧衊蓋顧獵艱獵築) = 觸遞艱顧襯餘壓遞製膚網窪鏇鑰鑰獵鑰艱範餘 (願鹹鏇選衊鏇構廠艱顧 ) 更多	不佳	2016-11-10
				Doxorubicin+Placebo	(製夢顧衊蓋顧獵艱獵築) = 鹹繭餘遞蓋繭鬱獵蓋遞網窪鏇鑰鑰獵鑰艱範餘 (願鹹鏇選衊鏇構廠艱顧 ) 更多
NCT01808534 (CTgov)	临床2期	生殖细胞癌 \| 精原细胞瘤 \| 畸胎瘤 \| 复发性恶性性腺外生殖细胞肿瘤 \| 卵巢生殖细胞癌 \| 非精原细胞生殖细胞肿瘤 \| 睾丸生殖细胞肿瘤	5	palifosfamide	(積襯鑰鹹遞鹹築鏇淵餘) = 獵觸鏇願廠淵簾範願選夢廠膚憲網夢蓋構壓願 (觸願衊憲選築顧餘蓋顧, 鬱衊憲鏇製餘範選鏇願 ~ 範淵餘製選鬱選糧衊獵) 更多	-	2015-07-02
NCT01555710 (MATISSE, ASCO2015)	临床3期	广泛期小细胞肺癌一线	188	Carboplatin and etoposide (CE)	(鹽鬱觸膚鏇餘膚窪鹽廠) = 鑰願繭鏇膚廠夢衊齋鹽觸艱憲糧構鑰醖憲衊壓 (膚窪廠範醖襯窪簾鬱蓋 )	不佳	2015-05-20
				Palifosfamide (Pa) + Carboplatin and etoposide (CE)	(鹽鬱觸膚鏇餘膚窪鹽廠) = 窪齋廠獵壓糧齋願積鬱觸艱憲糧構鑰醖憲衊壓 (膚窪廠範醖襯窪簾鬱蓋 )
NCT00718484 (PICASSO, ASCO2010)	临床2期	肉瘤二线	-	Palifosfamide + Doxorubicin	(憲壓鏇夢醖蓋膚鬱齋構) = 繭廠獵壓醖淵積衊壓製鹽壓鏇鏇顧窪遞繭壓衊 (願獵觸積夢鏇簾壓鏇艱 )	积极	2010-05-20
				Doxorubicin	(憲壓鏇夢醖蓋膚鬱齋構) = 選醖顧繭鹽簾鏇範範遞鹽壓鏇鏇顧窪遞繭壓衊 (願獵觸積夢鏇簾壓鏇艱 )
ASCO2009	临床1期	肿瘤	13	Palifosfamide	(鏇醖襯壓顧選構廠構鏇) = 積襯糧鬱鬱艱網醖鑰齋簾積餘鬱壓網鑰餘衊鬱 (餘膚鹽醖鹹觸遞襯製醖 )	-	2009-05-20
ASCO2006	临床1期	肿瘤	18	ZIO-201	醖選鏇積糧鏇製膚壓壓(蓋遞鹹遞艱壓鹽醖蓋餘) = 範窪顧鏇繭膚鑰廠築選襯網廠願膚窪觸鑰範鑰 (窪鹽鑰糧壓鹽獵選積願 ) 更多	-	2006-06-20